Neuroscience team wins grant to explore cognitive flexibility

Using a $5 million grant from the National Institutes of Health, a team of researchers in the UO’s Institute of Neuroscience hopes to better understand the neural mechanisms behind the ability to shift attention among differing tasks.

“Imagine an athlete or a musician or a student trying to focus on the task at hand, while ignoring the things going on around them and then suddenly switching their attention to something else,” said David McCormick, Presidential Chair and director of the Institute of Neuroscience. “This is something that we all use and depend on in our real lives. You don’t realize how important it is until it malfunctions.”

McCormick is a co-principal investigator on the five-year NIH grant to explore the phenomenon of cognitive flexibility. Funded through the BRAIN Initiative, the Obama-era program that aims to revolutionize the understanding of the human brain, the project involves neuroscientists from six UO research labs. Together, they will employ advanced research tools and techniques to shed light on how neural pathways enable behavioral flexibility.

“It’s kind of the culmination of a lot of different things that we’ve each worked on separately, and now it’s a matter of putting it all together into answering these questions,” said Cris Niell, professor of biology and co-principal investigator on the grant. “Together we’re studying vision and we’re studying hearing. We’re doing everything from watching the activity of hundreds to tens of thousands of neurons, either with advanced optics or the latest in electrical recording techniques. This massive amount of interesting and important data also requires advanced computational tools that tie it all together.”

Along with McCormick and Niell, the team includes biology professor Santiago Jaramillo, psychology professors Michael Wehr and Matt Smear, and Luca Mazzucato, a professor in the Departments of Biology and Mathematics, all members of the Institute of Neuroscience.

The team will begin by training mice in a series of tasks. They will observe changes in attention brought about by different sensory prompts, so a mouse focused on a visual task may be cued, through the presentation of a smell, to quickly change its focus to sounds while ignoring visual stimuli. Niell’s expertise in visual processes will meet with Jaramillo’s research on auditory coding, Wehr’s interest in the auditory cortex and Smear’s focus on olfactory function.

While mice are performing their tasks, the team will use advanced techniques such as wide-field imaging, which will enable them to view a large portion of the surface of the mice’s brains. Recording tens of thousands of blinking neurons generates tremendous amounts of data, which is where computational neuroscientist Mazzucato comes in. To help sift through the mountain of information, he will use methods from statistical physics, information theory, machine learning and other areas of expertise.

The project builds on McCormick’s research examining how a state of attention can modulate the function of the brain and Niell’s research showing how physical activity can enhance visual processing in mice. Niell and McCormick have previously explored similar questions about the behavioral state of animals and how their activity affects brain processing. Additionally, the project dovetails with Jaramillo’s research on neuronal circuits involved in behavioral flexibility and attention.

McCormick, who came to the UO in 2017 from Yale University, said the project is just the kind of collaborative research challenge that attracted him to Oregon in the first place. Tackling such a large-scale project required tapping into the full depth of expertise and equipment available in the Institute of Neuroscience.

“There are only a couple of other places in the world that have the number of people and skill sets and a critical mass like we do for this particular type of research,” McCormick said.

One of the questions the team hopes to answer is what specific processes are driving the attentional shifts in mice. There is some evidence that the systems that regulate behavioral and brain arousal or other activities may be involved, and the team will examine the role that acetylcholine, norepinephrine and other neurotransmitters play. In the later stages of the project they will shift from observing and gathering data to manipulating the mechanisms in mice using techniques such as optogenetics, which allows researchers to monitor and control the activity of brain cells with light signals.

Any kind of fundamental information the team can gain about how the brain processes information and moves it from one place to another is potentially valuable, and Niell said the research could have numerous uses down the road. There are potential implications for everything from improving people’s ability to focus on the tasks in their daily lives to addressing more serious conditions such as attention deficit disorder or even schizophrenia and some psychiatric diseases.

Niell said it could help explain other phenomena, including the so-called “cocktail party effect.” The phenomenon, which is sometimes described as selective attention or selective hearing, refers to the brain’s ability to dial into one conversation while tuning out multiple different conversations happening nearby.

What’s more, Niell said, the project has special resonance in our current era when so many of us are facing additional responsibilities and distractions.

“Many of us have kids at home doing school work and we’re trying to avoid scrolling on our phones to figure out who won the election and things like that,” Niell said. “This research is especially relevant now, when we are in this world where there’s just too many things going on for us.”

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